Here, we demonstrate for the first time that expression of human truncated tau protein, whose primary sequence was derived from paired helical filaments obtained from the brains of AD patients, is sufficient to induce dysfunction of LC neurons in vivo and this dysfunction is most likely followed by exaggerated synthesis of pro-inflammatory cytokines in brain structures innervated by the LC that are known to be affected by neuropathology in AD patients. The gene discussed is MAPT; the disease is Alzheimer disease.